TRANSCRIPTIONAL ACTIVATION OF HISTONE H1-DEGREES DURING NEURONAL TERMINAL DIFFERENTIATION

We have examined the central nervous system (CNS) of developing and ad ult transgenic mice carrying sequences upstream of the histone H1 degr ees gene fused to the E. coli beta-galactosidase gene (lac Z). The tra nsgene is induced in a subset of the neuronal population during postna tal development, coinciding with neuronal teminal differentiation. At postnatal day 9, the earliest time at which the transgene product can be detected, positive neurons are observed in the granular layer of th e cerebellar cortex and in the pyramidal fields of the hippocampus. Th e transgene is then induced in other areas of the CNS, such as the neo cortex, thalamus, hypothalamus, olfactory bulb, globus pallidus superi or and inferior colliculus, substantia nigra, pontine nuclei and brain stem. Induction is unrelated with determination and quiescence, which are essentially prenatal. The overlapping of the temporal and regiona l patterns of transgene activity with those of the endogenous protein shows that the accumulation of H1 degrees in differentiating neurons i s at least in part under transcriptional control. In the light of thes e results, the H1 degrees gene appears as the only mammalian histone g ene that specifically responds to terminal differentiation. However, n ot all terminally differentiated neurons express H1 degrees at detecta ble levels. For instance, Purkinje cells are negative. In neurons, ter minal differentatiation appears thus as a necessary, but not a suffici ent condition for increased H1 degrees expression.